This invention relates to compositions and methods for nutritional management of renal failure. In particular it is directed at novel amino acid compositions for meeting the specialized nutritional requirements of patients suffering renal failure and the attendant derangements of normal amino acid metabolism and dialysis-induced losses in the body's amino acid complement.
Renal failure may be classified as acute or chronic. Acute renal failure is characterized by an abrupt, often reversible impairment (partial or total) of renal function, manifested by inadequate urine formation. Acute renal failure usually appears rapidly--on the order of one to several days--either with or without prior renal dysfunction. Urine output may range from total anuria through stages of oliguria, to polyuria in the diuretic (recovery) phase.
Acute renal failure follows from a diversity of possible causes, which are divided into two categories: nephrotoxic injury and renal ischemia. Nephrotoxic injury results from sensitivity response or excessive and/or continuous exposure to drugs, chemicals, heavy metals, etc., which prove toxic to the renal tubular cells, while renal ischemia results from clinical situations causing hypovolemia, hypotension, and/or acute dehydation. Some commonly encountered etiologic factors include: complications of anesthesia, major surgery, obstetrical complications and trauma.
Patients with acute renal failure very often are subject to such complications as sepsis and hypercatabolism. The resulting secondary malnutrition and wasting has resulted in considerable attention being given to nutritional adjuncts to therapy. Previous principles called for severe or total restriction of protein intake to reduce uremia (azotemia). However, more recent therapy has combined very careful protein dosing (including the use of crystalline amino acids) to adequately nourish the patients, with prophylactic dialysis to control uremia.
In contrast with acute renal failure, chronic renal failure is characterized by a gradual destruction of the number of functional nephrons and thus gradual reduction of renal functional capacity. Given the initial reserve renal functional capacity, the kidney can adapt quite well as the disease progresses. Electrolyte balance is often well regulated, but nitrogenous substances (urea, creatinine) accumulate. Chronic renal failure may result from renal circulatory insufficiency, loss of effective renal mass, intrinisic functional disorders, and urinary tract obstruction.
Conservative management, including nutritional therapy, can be successful in prolonging the time before dialysis therapy is initiated. Patients with chronic renal failure are also often malnourished and wasted from anorexia, associated illnesses, unpalatable dietary regimens, uremic "toxins", altered nutrient needs, and the effects of dialysis. Restriction of protein over the long-term is commonly-accepted therapy, but it is difficult to enforce and dangerous, since it can promote chronic tissue wasting.
Instead of, or in conjunction with limiting protein intake the art has attempted to support renal failure patients by supplying amino acids alone in controlled amounts and proportions or as dietary supplements.
It is known to supply amino acids by parenteral or enteral routes for nutrition in renal failure, and to use mixtures of the eight essential amino acids alone (L-leucine, L-phenylalanine, L-methionine, L-lysine, L-isoleucine, L-valine, L-threonine, and L-tryptophan) or supplemented with various nonessential amino acids, many of which have been shown to be effectively essential in the circumstances of renal failure, e.g., histidine. Examples of such amino acid compositions are disclosed in U.S. Pat. No. 3,764,703, West German Offlegungsschriften Nos. 25 31 204, 25 30 246 and 26 33 948, Bergstrom et al., "Clin. Sci Mol. Med." 51: 589-99 (1976); Bergstrom et al., "Clin. Sci. Mol. Med." 54: 51-60 (1978); Furst et al., "Am. J. Clin. Nutr." 31: 1744-55 (1980); Motil et al., "JPEN" 4: 3235 (1980) and Piraino et al., Second Congress of the European Society of Parenteral and Enteral Nutrition. Newcastle Upon Tyne, September 1980.
None of the heretofore employed amino acid mixtures are considered by applicants to be of optimal benefit in nutritional support during renal failure, particularly concomitant with dialysis. A formulation has been needed which will produce the most favorable clinical response as measured by plasma and intracellular amino acid profiles approaching normal, protein turnover and nitrogen balance.
Accordingly it is an object of this invention to supply an amino acid composition which will contribute to the attainment of positive nitrogen balance.
It is another object to normalize both the intracellular and plasma amino acid concentrations in renal failure patients, including such patients undergoing frequent dialysis.
These and other objects of the invention will be apparent from the specification as a whole.